CN103524750A - Polyethylene glycol chitosan self-assembled nanoparticles and preparation method thereof - Google Patents
Polyethylene glycol chitosan self-assembled nanoparticles and preparation method thereof Download PDFInfo
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Abstract
The invention discloses polyethylene glycol-chitosan self-assembled nanoparticles and a preparation method thereof, belonging to the technical field of preparation of a functional material. Chitosan derivative with water solubility and biocompatibility is obtained by modifying chitosan by polyethylene glycol, so as to prepare the polyethylene glycol-chitosan self-assembled nanoparticles. The polyethylene glycol-chitosan self-assembled nanoparticles have the advantages that TEMED (tetramethylethylenediamine).HCL is taken as a diluent; EDC (dichloroethane) and NHS are taken as activating agents under a mild condition; the polyethylene glycol chitosan derivative with water solubility and biocompatibility is prepared by grafting mPEG-COOH on CS in a covalent coupling manner and modifying the chitosan by PEG (polyethylene glycol), so that the nanoparticles can be formed in a water solution in a self-assembling manner.
Description
Technical field
The invention belongs to functional materials preparing technical field.
Background technology
Chitosan is the unique alkaline polysaccharide of nature, is the product of chitin N-deacetylation, in shell, shrimp shell crab shell, arthropods, annelid, mollusk, exists in a large number.That chitosan has is nontoxic, physiologically acceptable, biological degradation and the advantage such as antibiotic, is widely used in the fields such as biology, medical science.Yet, due in molecule and the existence of intermolecular powerful hydrogen bond, cause the water insoluble and physiological environment of chitosan, greatly limited its application, therefore, the exploitation with the chitosan derivatives of specified property receives much concern.
In biology, medical field, the preparation method who can be used as the chitosan nano particle of macromolecular drug and the application of bioactive macromolecule carrier mainly contains: covalent cross-linking method, Precipitation method, self-assembly etc.Covalent cross-linking method can affect the release of macromolecular substance; Precipitation method is inhomogeneous reaction, and preparation condition is harsh.Therefore prepare a kind of amphipathic chitose with water-soluble and good biocompatibility, by molecule self-assembly in the aqueous solution, form the nanoparticle of size uniform, to realize embedding and the release of macromolecular drug and bioactive macromolecule, having great importance, is that chitosan is as the desirable approach of green of pharmaceutical carrier.
Summary of the invention
The object of the invention is to propose a kind of polyoxyethylene glycol chitosan self-assembled nanometer grain that can overcome above chitosan and chitosan nano preparation method defect.
Molecular structural formula of the present invention is:
Wherein, n=2598, and x=300.
The aqueous dispersion of this nanoparticle is stable, and size homogeneous, is suitable for macromolecular drug, active macromolecular embedding and release, be expected to become have the bioactive macromolecule of application prospect, the ideal carrier of medicament slow release.
The present invention also proposes the preparation method of above polyoxyethylene glycol chitosan self-assembled nanometer grain.
Comprise the following steps:
1) prepare mPEG-COOH: first mPEG is dissolved in to dry pyridine, then add succinyl oxide, isothermal reaction is to finishing, remove again pyridine, gained solid dissolves through toluene, slowly adds normal hexane, to product Precipitation under magnetic agitation, crude product, through dialysis, lyophilize, can obtain molecular weight and be 2000 mPEG-COOH;
2) CS that is 500KDa by molecular weight is dissolved in aqueous acetic acid, then the TEMEDHCL that is 4.7 with pH dilution CS aqueous acetic acid, obtains CS diluent;
3) by EDC hydrochloride and N-N-N-Hydroxysuccinimide and step 2) the CS diluent made mixes, add again mPEG-COOH, under 35 ℃ of constant temperatures, stir and control pH value of reaction system and maintain 4～6, make the thick product of PEG-CS;
4) PEG-CS crude product is placed in to dialysis tubing and dialyses, lyophilize obtains PEG-CS white solid;
5) PEG-CS white solid is scattered in 37 ℃ of distilled water, obtains polyoxyethylene glycol chitosan self-assembled nanometer grain.
The present invention obtains and has the chitosan derivatives of water-soluble and biocompatibility with polyethyleneglycol modified chitosan, thereby prepares polyoxyethylene glycol chitosan self-assembled nanometer grain.
Advantage of the present invention is: under gentle condition, take TEMEDHCL as thinner, EDC and NHS are activator, by covalent coupling, mPEG-COOH is grafted on CS, with PEG beautify chitosan, prepare a kind of polyoxyethylene glycol chitosan derivatives with water-soluble and good biocompatibility, can in the aqueous solution, self-assembly form nanoparticle.
In addition, in step 1), the molar ratio of described mPEG and succinyl oxide is 1:1.2, to guarantee that mPEG is converted into mPEG-COOH completely; Described constant temperature is 60 ℃, reacts 2h, can guarantee the homogeneity of heating, makes to react completely.
The concentration of aqueous acetic acid step 2) is 2% w/v, and the feed ratio of described CS and aqueous acetic acid is 1g ︰ 6ml.Can guarantee that CS is dissolved in aqueous acetic acid completely.
In step 3), in mPEG-COOH and diluent, the mol ratio of CS is adjustable, to obtain the PEG-CS of certain graft(ing) degree.
In order to guarantee that mPEG-COOH activates completely, promote subsequent reactions, in step 3), EDC(1-(3-dimethylamino-propyl)-3-ethyl-carbodiimide hydrochloride), NHS(N-N-N-Hydroxysuccinimide) and the mixing quality ratio of mPEG-COOH be 16～77 ︰ 1～46 ︰ 8～400.
The molecular weight cut-off of dialysis tubing described in step 4) is 25KDa, and dialysis time 4 days guarantees the small-molecule substance that has neither part nor lot in reaction to dialyse away completely, to obtain pure products.
Accompanying drawing explanation
The infrared spectrogram of Fig. 1 polyoxyethylene glycol chitosan PEG-CS (PEG:CS=5:1).
The fluorescence spectrum figure of Fig. 2 pyrene in different concns PEG-CS (PEG:CS=5:1).
The I of Fig. 3 pyrene
1/ I
3value is with PEG-CS (PEG:CS=5:1) change in concentration graph of relation.
Fig. 4 polyoxyethylene glycol chitosan PEG-CS (PEG:CS=5:1) self-assembled nanometer grain TEM photo.
Embodiment
One, embodiment 1: the polyoxyethylene glycol chitosan self-assembled nanometer grain of preparation PEG:CS=5:1:
1, mPEG-COOH's is synthetic:
Take 5g mPEG and put into round-bottomed flask, with 25ml dry pyridine, dissolve, then add 0.3g succinyl oxide, after 60 ℃ of isothermal reaction 2h, at 45 ℃, with Rotary Evaporators underpressure distillation, remove most pyridines.Gained solid dissolves with 30ml toluene, on magnetic force heating stirrer, constantly stirs, and slowly adds 40ml normal hexane precipitation agent, separates out to product.Dialysis tubing dialysis is four days for crude product, and the gained material lyophilize of then dialysing obtains product, can obtain molecular weight and be 2000 mPEG-COOH.
2, preparation Pegylation chitosan PEG-CS(PEG:CS=5:1):
Take 1g CS(500KDa) be dissolved in 6 ml acetic acid (2 %, w/v) in, the TEMEDHCL that is 4.7 with 20 ml pH dilution, join in there-necked flask, then add 0.77 mg EDC and 0.46 mg NHS, after 30min, by mPEG-COOH and CS mol ratio, be that to take molecular weight be that the 1g CS(mol ratio that 2000 20 mg mPEG-COOH and molecular weight are 500KDa is 5:1 to 5:1), join in there-necked flask, 35 ℃ of waters bath with thermostatic control, stirring reaction 36 h, control pH 4～6 in reaction process.
Crude product is placed in dialysis tubing and dialyses 4 days, and lyophilize obtains Pegylation chitosan (PEG:CS=5:1) solid.
3, the preparation of Pegylation chitosan PEG-CS (PEG:CS=5:1) self aggregation assemble nanometer grain:
Pegylation chitosan PEG-CS solid is scattered in distilled water 37 ℃ time, obtains polyoxyethylene glycol chitosan self-assembled nanometer grain.
FT-IR BRUKER, Tensor27 spectrometry.As shown in Figure 1, by contrast, can find out 1074 cm on the IR spectrogram of PEG-CS
-1the relative intensity of left and right ehter bond absorption peak, apparently higher than chitosan, can be observed 1632 cm simultaneously
-1, 1522 cm
-1the appearance of place's acid amides I bands of a spectrum and acid amides II bands of a spectrum, proves that chitosan and mPEG-COOH have occurred to react.
By Fig. 1, learn that mPEG is successfully grafted to chitosan, under the effect of EDC, there is acylation in the carboxyl on mPEG-COOH and the amino on chitosan, forms amido linkage, and mPEG is grafted to chitosan, and PEG-CS molecular structure as shown in Figure 2.
Take pyrene as fluorescent probe, the gathering behavior with fluorescence spectrum (F4500 type fluorescence meter) research PEG-CS nano particle in the aqueous solution.As shown in Figure 2,3, in the PEG-CS of lower concentration solution, the I of pyrene
1/ I
3value approaches the I of pyrene in pure water
1/ I
3value 1.72, when PEG-CS concentration is 0.5 ~ 1.4 mg/mL, I
1/ I
3value significantly decreases, when PEG-CS concentration is greater than 1.4 mg/mL, and I
1/ I
3be worth constantly in 1.20 left and right, although be less than the value in pure water, interface is still very hydrophilic.PEG-CS placement is repeated to experiment after 7 days obtained identical result, show that polyoxyethylene glycol chitosan self-assembled nanometer grain has good stability.
Fig. 4 is the photo after phospho-wolframic acid dyeing for PEG-CS self-assembled nanometer grain, Tecnai-12 type transmission electron microscope observation.PEG-CS self-assembled nanometer grain is regular spherical as can be seen from Figure, and particle diameter is 35 ± 5nm approximately, has very bright and clean surface and good regularity.
Prepared Pegylation chitosan self-assembled nanometer grain can be used as pharmaceutical carrier, increases solubleness, metabolic stability and the body-internal-circulation time of medicine.Can successful load insulin as prepared herein Pegylation chitosan nano, encapsulation rate can reach more than 85%.
Molecular structural formula is:
Wherein, n=2598, x=300.
Two, embodiment 2: the polyoxyethylene glycol chitosan self-assembled nanometer grain of preparation mPEG:CS=1:10:
1, mPEG-COOH's is synthetic:
Take 5g mPEG and put into round-bottomed flask, with 25ml dry pyridine, dissolve, then add 0.3g succinyl oxide, after 60 ℃ of isothermal reaction 2h, at 45 ℃, with Rotary Evaporators underpressure distillation, remove most pyridines.Gained solid dissolves with 30ml toluene, on magnetic force heating stirrer, constantly stirs, and slowly adds 40ml normal hexane precipitation agent, separates out to product.Dialysis tubing dialysis is four days for crude product, and the gained material lyophilize of then dialysing obtains product, can obtain molecular weight and be 2000 mPEG-COOH.
2, the preparation of Pegylation chitosan PEG-CS (PEG:CS=1:10):
Take 1g CS (500KDa) and be dissolved in 6 ml acetic acid (2 %, w/v) in, with 20 ml TEMEDHCL(pH 4.7) dilution, join in there-necked flask, then add EDC (0.016 mg) and NHS (0.01 mg), after 30min, in the ratio of mPEG:CS=1:10, take CS(molar mass that mPEG-COOH that 0.4 mg molecular weight is 2000 and 1g molecular weight are 500KDa than being 1:10), join in there-necked flask, 35 ℃ of waters bath with thermostatic control, stirring reaction 36h, controls pH 4-6 in reaction process.
Crude product is placed in dialysis tubing and dialyses 4 days, and lyophilize obtains Pegylation chitosan (PEG:CS=1:10) solid.
3, the preparation of Pegylation chitosan PEG-CS (PEG:CS=1:10) self aggregation assemble nanometer particle:
Pegylation chitosan PEG-CS (PEG:CS=1:10) solid is scattered in distilled water 37 ℃ time, obtains polyoxyethylene glycol chitosan self-assembling nanoparticles.
Molecular structural formula is:
Wherein, n=2598, x=300.
Claims (6)
1. polyoxyethylene glycol chitosan self-assembled nanometer grain, molecular structural formula is:
Wherein, n=2598, x=300.
2. the preparation method of polyoxyethylene glycol chitosan self-assembled nanometer grain as claimed in claim 1, comprises the following steps:
1) prepare mPEG-COOH: first mPEG is dissolved in to dry pyridine, then adds succinyl oxide, isothermal reaction is to finishing, remove pyridine, gained solid dissolves through toluene, slowly adds normal hexane under magnetic agitation, to product Precipitation, crude product obtains mPEG-COOH through dialysis, lyophilize;
2) CS that is 500KDa by molecular weight is dissolved in aqueous acetic acid, then the TEMEDHCL that is 4.7 with pH dilution CS aqueous acetic acid, obtains CS diluent;
3) by EDC hydrochloride and N-N-N-Hydroxysuccinimide and step 2) the CS diluent made mixes, add again mPEG-COOH, under 35 ℃ of constant temperatures, stir and control pH value of reaction system and maintain 4～6, make the thick product of PEG-CS;
4) PEG-CS crude product is placed in to dialysis tubing and dialyses, lyophilize obtains PEG-CS white solid;
5) PEG-CS white solid is scattered in 37 ℃ of distilled water, obtains polyoxyethylene glycol chitosan self-assembled nanometer grain.
3. preparation method according to claim 2, is characterized in that in step 1), and the molar ratio of described mPEG and succinyl oxide is 1:1.2, and described temperature of reaction is 60 ℃ of constant temperature, reaction 2h.
4. preparation method according to claim 2, is characterized in that step 2) described in the concentration of aqueous acetic acid be 2% w/v, the feed ratio of described CS and aqueous acetic acid is 1g ︰ 6ml.
5. preparation method according to claim 2, the mixing quality ratio that it is characterized in that the hydrochloride of EDC described in step 3), N-N-N-Hydroxysuccinimide and mPEG-COOH is 16～77 ︰ 1～46 ︰ 8～400.
6. preparation method according to claim 2, the molecular weight cut-off that it is characterized in that dialysis tubing described in step 4) is 25 KDa, dialysis time 4 days.
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| CN104491844A (en) * | 2014-12-02 | 2015-04-08 | 扬州大学 | Production method of insulin oral sustained-release preparation |
| CN105640922A (en) * | 2016-01-25 | 2016-06-08 | 扬州大学 | Preparation method of novel arsenic trioxide preparation with positive charges and liver targeting effect |
| CN106750336A (en) * | 2016-12-08 | 2017-05-31 | 福州大学 | A kind of preparation method of glucan co polyethylene glycol nanoparticles |
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Non-Patent Citations (3)
| Title |
|---|
| 周瑞梅: "聚乙二醇单甲醚改性壳聚糖的制备及其性能研究", 《中国优秀硕士学位论文全文数据库 工程科技I辑》 * |
| 魏晓红等: "PEG化壳聚糖%2fDNA自组装复合物的制备、表征和体外Hela细胞转染研究", 《高等学校化学学报》 * |
| 魏晓红等: "PEG化壳聚糖%2fDNA自组装复合物的制备、表征和体外Hela细胞转染研究", 《高等学校化学学报》, vol. 24, no. 11, 30 November 2003 (2003-11-30), pages 1993 - 1996 * |
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| CN111484568B (en) * | 2019-01-25 | 2021-12-14 | 中国科学院理化技术研究所 | Chitosan-antibacterial polypeptide graft polymer and preparation method and application thereof |
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